Caffeine overcomes genistein-induced G2/M cell cycle arrest in breast cancer cells
Caffeine overcomes genistein-induced G2/M cell cycle arrest in breast cancer cells
复制标题
咖啡因克服金雀异黄素诱导的乳腺癌细胞 G2/M 细胞周期停滞
DOI：
10.1080/01635580701861785
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发表时间：
2008-05-01
影响因子：
2.9
通讯作者：
Xu, Jida
中科院分区：
文献类型：
--
作者：
Li, Zhong;Liu, Wen;Xu, Jida
虽然染料木黄酮抑制肿瘤细胞生长是通过不同类型的细胞周期阻滞介导的，但其对细胞周期相关基因的调控尚不清楚。在这项研究中，染料木黄酮引起的浓度依赖性的生长抑制在非依赖于乳腺癌细胞株MDA-MB-435 S。流式细胞仪分析表明，染料木黄酮诱导细胞在细胞周期的G2/M期的浓度依赖性的积累。咖啡因可增强染料木素对细胞增殖的抑制作用。单独的咖啡因对细胞周期的各阶段没有明显的影响，但3 mM的咖啡因完全消除了染料木黄酮诱导的G2/M细胞周期阻滞。cDNA微阵列被用来研究染料木黄酮诱导的，咖啡因阴性的G2/M期阻滞的机制。我们确定了12个基因，它们对染料木黄酮和咖啡因治疗有相反的反应。其中5个基因被染料木黄酮上调，咖啡因下调; 7个基因被染料木黄酮下调，咖啡因上调。咖啡因拮抗染料木黄酮诱导的乳腺癌细胞G2/M期阻滞，可增加其对染料木黄酮的敏感性，增强染料木黄酮对细胞生长的抑制作用。对染料木黄酮和咖啡因具有相反反应的基因可能参与细胞周期的G2/M期的调节。
Although inhibition of tumor cell growth by genistein is mediated by different types of cell cycle arrest, its regulation of genes related to the cell cycle is not clear. In this study, genistein caused a concentration-dependent growth inhibition in the hormone-independent cell line MDA-MB-435S. Flow cytometric analysis showed that genistein induced a concentration-dependent accumulation of cells in the G2/M phase of the cell cycle. Caffeine enhanced the inhibition of cell proliferation induced by genistein. Caffeine alone did not have an appreciable effect on the phases of the cell cycle, but caffeine at 3 mM completely eliminated genistein-induced G2/M cell cycle arrest. cDNA microarrays were used to investigate the mechanism of genistein-induced, caffeine-negated G2/M arrest. We identified 12 genes, which had opposite responses to genistein and caffeine treatments. Among these, 5 genes were upregulated by genistein and downregulated by caffeine; 7 genes were downregulated by genistein and upregulated by caffeine. Reversal by caffeine of genistein-induced G2/M phase arrest in breast cancer cell lines could increase their sensitivity to genistein and enhance genistein-induced inhibition of cell growth. Genes that have opposite responses to genistein and caffeine may be involved in regulation of the G2/M phase of the cell cycle.